Compounds of the diamino-acridinhjm



Patented Jan. 24, 1939 UNITED STATES PATENT OFFICE COMPOUNDS OF THE D-IAMINO-ACRID'INIUM SERIES AND PROCESS THEM 0F PREPARING No Drawing. Application April 17, 1936, Serial No. 75,016. In Germany April 20, 1935 7 Claims. (01. 260-279) The present invention relates to compounds of the diamino-acridinium series and to a process of preparing them.

We have found that the compounds from 3.6- diamino-acridinium compounds and aliphatic, aliphatic-aromatic and hydroaromatic ketones described in U. S. Patent No. 2,044,892 of June 23, 1936, to Otto Sievers, may very readily be split up. Already after a short boiling with water the ketones begin to escape and when boiling is continued there is obtained an aqueous solution of the 3.6-diamino-acridinium hydroxides:

wherein X stands for alkyl or benzyl and Y for hydrogen or alkyl low in the series. These hydroxides may be transformed into the corresponding ethers by means of alcohols, phenols, alcoholates or phenolates, or into the corresponding acridinium salts by means of salts or acids. Dilute acids split up the ketones gradually when the compounds are allowed to stand at room temperature and very quickly when boiled. By applying calculated amounts of acid there may be obtained neutral, or if dibasic or polybasic acids or the salts thereof are used, acid acridinium compounds of the corresponding acids.

Instead of the acids there may be used the salts thereof formed with the aid of readily vola tile bases, for instance, ammonia, aniline, methylamine, dimethylaniline; there may also be used the acid amides, such as formamide or acetanilide which, on boiling with water, yield the corresponding ammonium salts or amine salts, the acridinium hydroxides displacing the readily volatile amines. The latter pass over with the water vapor. The salt formation at the amino nitrogen is thus avoided, since the transformation only takes place until all of the acridinium hydroxides are converted into the acridinium salt whereas an excess of the amine salt remains dissolved in an unaltered condition. The reaction, for instance, takes place according to the following scheme:

3.6-diamino-l0-methy1- C acridiniumacetone compound HzN /N NH, OH: R

wherein R stands for any acid radical. Owing to the great variety of possible methods it is possible to obtain in a simple way and in an entirely pure form any desired acridinium compound, particularly also compounds which are very readily soluble and cannot be obtained by another method. There may also be obtained acridinium compounds of polybasic acids the other acid radicals of which still contain metals, for instance according to the following scheme:

The products thus obtained have very good disquantity of animal charcoal. The escaping acetone is distilled. Since the acridinium hydroxide obtained is very oxidizable a strong current of nitrogen is passed through the flask. When about 1200 cc. of liquid are distilled, the separation of acetone ceases. The whole is filtered into a measuring flask, made up to 2000 cc. and the air is displaced from the flask with the aid of nitrogen. In this state the solution is stable for an unlimited time.

2. 500 cc. of the solution prepared as described in Example 1 are mixed with a solution of 8 grams of sodium metavanadate in cc. of water. The 3.6-diamino-IO-methylacridinium vanadate is precipitated from the solution which becomes strongly alkaline to phenolphthalein. It is a redbrown powder which dissolves in water in the proportion of 114000.

3. To a solution of 8 grams of potassium chlorate in 100 cc. of water there are added 500 cc. of acridinium hydroxide solution prepared as described in Example 1. The 3.6-diamino-10- methylacridinium chlorate precipitates with formation of free caustic potash solution in the form of a brown-red powder. It dissolves in water in the proportion of 1:250.

4. 14 grams of 3.6-diamino-lo methylacridiniumacetone compounds are heated ,for 3 hours on a water bath with 400 cc.of water and 10 grams of quinic acid. A clear solution is obtained. Animal charcoal is added to the solution; the water is evaporated and the product is again dissolved with cc. of hot water, filtered and made up to 200 cc. A solution of 10 per cent. strength of the 3.6-diamino-IO-methylacridinium-hexahydrotetraoxybenzoate is thus obtained from which this compound may easily be isolated. It forms a brick red crystalline powder which is very readily soluble in water, "readily soluble in methyl alcohol and ethyl alcohol, sparingly soluble in acetone and completely insoluble in ether, ethyl acetate and benzene. 7

5. 10 grams of camphoric acid are dissolved in 400 cc. of water and 5000. of normalcaustic soda solution. 14 grams of 3.6-diamino- 10-methylacridiniumacetone compound and a small quantity of animal charcoalare added to the solution. The whole is heated on the water-bath until the undesirable foaming has ceased;-the solution is then boiled for one hour and finally evaporated to dryness. It is then dissolved with 150 cc. of hot water, filtered and made up to 220 cc. The solution contains 10 per cent of the sodium salt of 3.6-diamino-IO-methyIacridiniumcamphoric acid compound which may be isolated in the usual manner. It is a yellow powder which is very readilysoluble in water, readily soluble in methyl alcohol and ethyl alcohol, sparingly soluble in butanol, scarcely soluble in acetone and insoluble in ethyl acetate, benzene and ether. The compound corresponds with the following formula:

6. ligrams of 3.6-diamino-IO methyIacridini ually obtained, acetone and ammonia being evolved. It is evaporated to dryness, dissolved in a small amount of water, again evaporated, again dissolved with addition of animal charcoal, filtered and made up to cc. A solution of 10 per cent. strength of 3.6-diamlno-lO-methylacridinium sodium phosphate of the formula:

Na is obtained.

'7. 14 grams of 3.6-diamino-10-methylacridiniumacetone compound are evaporated in an open vessel with 400 cc. of water and 1.9 grams of ammonium fluoride; the residue is taken up with water, filtered with animal charcoal and made up to 240 cc. 1A solution 01 5 per cent strength of 3.6-diamino-IO-methylacridinium fluoride is obtained.

8. A mixture of 15 grams of 2.7-dimethyl-3.6-

diamino-10-methylacridiniumaceton-e compound, 200 cc. of water and '7 grams of aniline hydrochloride is distilled with steam; as soon as neither aniline nor acetone passes over, the yellow solution is filtered with a small quantity of animal charcoal and cooled. The '2.'7-dimethyl-3.6-diamino-IO-methylaoridinium chloride separates in a completely pure form.

' 9. 16 grams of 3.6-diamino-IO-methylacridiniumcyclohexanone compound are boiled with 2 liters of water and 12 grams of para-oxybenzoic acid until the evolution of cyclo hexanone has ceased. The whole is mixed with animal charcoal and filtered The 3.6-diamino-IO-methylacridinium-para-oxybenzoate which crystallizes on cooling forms orange-red needles which dissolve in water in the proportion of 1:2500.

10. 14 grams of 3.6-diamino-10-methylacridinlumacetone compound are heated for 2 hours on the water-bath with 400 cc. of water, some animal charcoal and 11 grams of 2-pyridone-5-arsinic acid. The solution obtained is then evaporated to dryness in an open vessel. The residue is taken up with 100 cc. of hot water, the solution is filtered and cooled. The 3.G-diamino-10-methylacridinium-2-pyridone-5-arsinate crystallizes in the form of light-yellow needles which dissolve in water in the proportion of 1 :50; they are insoluble in the usual organic solvents except in methyl alcohol and ethyl alcohol.

11. 14.0 grams of 3.6-diamino-10methylacridiniumacetone compound are heated for 5 hours on the water-bath with 2 liters of water and 30 grams of acetamide. The whole passes into solution with evolution of acetone and ammonia. The solution is evaporated almost todryness and the 3.6-diamino-10-methylacridiniumacetate is precipitated with acetone in the form of a red powder. r

12. 6 grams of pyrocatechol are mixed with 100 cc. of the solution of 3.6-diamino-10-methylacridinium hydroxide prepared as described in Example 1. A thick yellow precipitate is obtained which is thoroughly stirred. 400 cc. of the solution of'the base are then gradually added. The yellow precipitate is filtered with suction, washed with a small quantity of water and then with a mixture of equal parts of acetone and ether,

Br Br 14. 15 grams of the 3.6-diamino-10-oxyethy1- acridinium-cyclohexanone compound are boiled with 200 cc. of water, nitrogen being passed through until complete dissolution has occurred. The solution evaporated to 100 cc. is filtered and mixed with a solution of 6 grams of pyrocatechol in 50 cc. of water. The 3.6-diamino-10-oxyethylacridinium-ortho-oxyphenolate separates in the form of a yellow precipitate. It has the formula:

zN N NH CHz-CHrOH 15. 28 grams of the 3.6-diamino-10-methy1- acridiniumacetone compound are boiled for 3 hours in the reflux apparatus with 25 grams of benzyl alcohol. The 3.6-diamino-IO-methylacridinium-benzyl alcoholate of the formula:

HZN/ N NE:

C Ha

OCHFCGHE charcoal; on addition of ether the 2.7-dimethyl- 3.6-diamino--methylacridinium formate is precipitated in the'form ofa red crystalline powder which is soluble to an almost unlimited extent in cold water to a solution having an extraordi-v narily strong green fluorescence.

17. 3.5 grams of glutamic acid are dissolved in 500 cc. of the solution of 3.6-diamino-10-methylacridinium hydroxide prepared as described in Example 1. After filtration the whole is made up to 375 cc. There is thus obtained a solution of 4 per cent. strength of 3.6-diamino-10-methylacridiniumglutaminate of the formula:

If only 250 cc. of the solution of the acridinium hydroxide are used the mono-glutaminate is obtained.

In this manner even the most sensitive acids may readily be transformed into their 3.6-diamino-lO-alkylacridinium salts.

We claim:

1. The process which comprises heating with water a compound obtainable by causing a compound of the following general formula:

wherein R stands for a member of the group consisting of alkyl and benzyl, X stands for the anion of a strong mineral acid and both Ys stand for a member of the group consisting of hydrogen and lower alkyl, to act upon a compound selected from the group consisting of aliphatic, aliphaticaromatic and hydroaromatic ketones in the presence of caustic alkali.

2. The process which comprises heating with Water a compound obtainable by causing a compound of the following general formula:

HzN NH:

wherein R stands for a member of the group consisting of alkyl and benzyl, X stands for the anion of a strong mineral acid and both Ys stand for a member of the group consisting of hydrogen and lower alkyl, toact upon a compound selected from the group consisting of aliphatic, aliphaticaromatic and hydroaromatic ketones in the presence of caustic alkali, the heating process being performed in the presence of a compound selected from the group consisting of acids, acid salts, acid amides or salts of volatile bases.

3. The process which comprises heating with water the compound obtainable by causing the 3.6-diamino-IO-methylacridinium chloride to act upon acetone in the presence of sodium hydroxide.

4. The process which comprises heating with 7. The compounds of the following formula:

wherein R stands for a radical of camphoric acid, said compounds being colored powders readily soluble in water, methyl alcohol and ethyl alcohol and diflicultly soluble in other organic solvents.

MAX BOCKMI'THL.

OTTO SIEVERS. 

